Clinical Trials

Hansa Medical is currently evaluating imlifidase in HLA-sensitized kidney transplant patients. Full details of the clinical program are available through a central database. Visit clinicaltrials.gov for clinical study information on imlifidase.

If you are interested in getting involved in a clinical study, please talk to your physician. They will be able to advise you on whether you would be eligible to enroll into a study and if participation could be right for you.

GBS is an acute autoimmune disease in which the peripheral nervous system is attacked by the immune system and IgG­-antibo­dies. It affects one in 100,000 people annually. While patients are typically treated with either IVIg or plasmapheresis, there remains a significant unmet medical need. In February 2018, imlifidase received Orphan Drug Designation from the FDA for the treatment of GBS.

A Phase 2 study of imlifidase in Guillain Barré Syndrome (GBS) was initiated in the second quarter of 2019. The Phase 2 study will recruit up to 30 patients from approx­imately ten European sites over 18 months. The study is an open­-label, single arm, multi­center study evaluating the safety, tolerability and efficacy of imlifidase in GBS patients in combination with standard of care intravenous immunoglobulin (IVIg).

During 2013 and 2014, Hansa Medical conducted a clinical first-in-human Phase 1 study. The study was a randomized placebo controlled dose-escalation study with 29 (20 active plus 9 placebo) healthy subjects. The objectives were to assess safety, efficacy in IgG cleavage, pharmacokinetics and immunogenicity of imlifidase following intravenous administration. The starting dose was 0.01 mg/kg BW and the highest dose group received 0.24 mg/kg BW. Imlifidase was considered safe and it effectively degraded the plasma IgG. In July 2015, the results from the Phase 1 study was published in PLOS ONE.

Based on the data from this study, it was decided to move from healthy subjects into patients where it is possible to measure not only imlifidase effect on plasma IgG but also the effect on specific pathogenic IgG. The Phase 1 data suggested that imlifidase could prove to be a therapeutic option in several clinical conditions.

During 2014 and 2015, the first clinical Phase 2 study with imlifidase treatment in sensitized patients was conducted and completed.

The study was a dose-finding study, and the intention was not to transplant patients by means of imlifidase treatment. There were eight dialysis patients, ranging from very highly and broadly immunized to more moderately immunized, included in the study. One group of patients was given 0.12 mg/kg BW and one group received 0.25 mg/kg BW imlifidase, and the patients were followed for two months after treatment.

The effect was measured as level of HLA antibodies, cytotoxic cross-match reactivity against hypothetical donors and level of IgG in serum/blood at different time-points after imlifidase treatment. Taken into account the efficacy of the drug and the medical need for a treatment of sensitized patients, we conclude that the risk-benefit favors imlifidase for desensitization prior to transplantation.

The patients participating in this study were not intended for trans­plantation under the study protocol. However, the patients were not removed from the waiting list, and the second patient in the study was transplanted with an incompatible kidney just after completing imlifidase treatment. Before imlifidase treatment the cross match between donor and recipient was positive, but after treatment it was turned negative and the patient was eligible for transplantation. Stable graft function has been maintained for more than one year with normal creatinine and no rejection episodes.

Phase 2 in Sweden (Completed)

In July 2015, a Phase 2 study in sensitized patients was initiated in Sweden and in December 2016 the study was successfully completed. The study has included ten sensitized patients on the waiting list for transplantation and the study allowed dose escalation. The objectives was to investigate both effect on HLA-antibodies and the safety of imlifidase in the transplantation setting. The patients have received a single dose of imlifidase which have enabled kidney transplantation i all patients. Each patient has been followed for six months. The primary and secondary objectives were met with imlifidase (IdeS) in the study.

Investigator sponsored Phase 1/2 in Los Angeles (Completed)

In September 2018, an investigator sponsored study using imlifidase (IdeS) was run by Professor Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles was finalized.

Professor Jordan has previously developed a desensitization protocol that allows transplantation of highly sensitized patients using kidneys from deceased donors, a procedure that is very difficult using other protocols based on plasmapheresis. The protocol is based on the use of alternating high dose intravenous gamma globulin and anti-CD20 treatments in order to lower the levels of anti-HLA antibodies and to prevent rebound of antibodies after incompatible transplantation. The patients are kept in the program for many months waiting for an organ offer from a deceased donor.

Professor Jordan has investigated imlifidase in combination with the high dose intravenous gamma globulin and anti-CD20 procedure. The study enrolled 17 patients and the patients has been followed for six months. The objectives of the study has been to investigate both efficacy (i.e. decrease in PRA, reduction in HLA antibody levels and reduction in AMR frequency) and safety of imlifidase.

Results from the study demonstrae that the imlifidase treatment enabled life-saving transplants in all 17 patients. Graft survival at study completion, six months post-transplantation, was 94%.

The Phase 2 study, which was completed in September 2018, enrolled 18 highly sensitized patients awaiting kidney transplantation. Patients included in this study had either failed previous attempts of desensitization or the currently available methods were considered insufficiently effective.

The study is entitled “A Phase II Study to Evaluate the Efficacy of imlifidase (IdeS (IgG endopeptidase)) to Desensitize Transplant Patients with a Positive Crossmatch Test” with the short name Highdes. The primary objective of the study has been to assess the efficacy of imlifidase in creating a negative crossmatch test in highly sensitized patients with a positive crossmatch test to their available donor. Converting the crossmatch test enables transplantation in patients who would otherwise not qualify for transplantation.

The study has also evaluated safety, kidney function and immunogenicity during a 6-month follow-up period. The Highdes-study was initiated in October 2016 and completed in September 2018.

Five sites have recruited patients to the Highdes study:

Cedars-Sinai Medical Center in Los Angeles, USA

The Johns Hopkins Hospital in Baltimore, USA

NYU Langone Medical Center in New York, USA

Necker Hospital in Paris, France

Uppsala University Hospital in Uppsala, Sweden

Results from the study demonstrate that the imlifidase treatment enabled life-saving transplants in all 18 patients. Graft survival at study completion, six months post-transplantation, was 89%.

Acute AMR is one of the most challenging adverse events after kidney transplantation, occurring in 10-15% of patients, and is the main cause for graft dysfunction. In the U.S. and Europe, there are approximately 40,000 patients who receive kidney transplants annually and approximately 400,000 who currently live with a kidney transplant. There is no approved treatment for acute AMR in heart, lung, kidney, liver and bone marrow transplants, and it remains a significant unmet medical need associated with loss of graft function.

As we have demonstrated in four Phase 2 studies of imlifidase to enable kidney transplantation for highly sensitized patients, imlifidase is effective in inactivating IgG. Imlifidase has the potential to effectively treat acute AMR and prevent the devastating loss of a transplanted kidney.

The Phase 2 study will recruit approximately 30 patients from eight sites in the U.S., France, Sweden, Austria and Australia over 2019/early 2020. The study is a randomized, open-label, multi-center, active control study designed to evaluate the safety and efficacy of imlifidase in eliminating donor specific antibodies (DSAs) in the treatment of active episodes of acute AMR in kidney transplant patients.

20 subjects will be randomized to receive imlifidase treatment, one intravenous dose of 0.25mg/kg. The 10 subjects in the active control arm will receive 5-10 sessions of plasma exchange (PE). Efficacy and safety will be monitored over a 6-month period post treatment.

More information about the study is available at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03897205) under the study title “A Randomized, Open-Label, Multi-Centre, Active Control Study Investigating the Efficacy and Safety of Imlifidase in Eliminating Donor Specific Anti-HLA Antibodies in the Treatment of Active Antibody-Mediated Rejection in Kidney Transplant Patients”.

Anti­GBM antibody disease, also known as Goodpasture’s disease, is a rare, acute autoimmune disease where autoantibodies directed against type IV collagen cause acute inflammation of the kidney and/or the lungs. In severe anti­GBM, the disease may progress to renal failure or death. Anti­GBM antibody disease affects one in a million patients annually, and less than one third of the patients survive with preserved kidney function after six­months follow­up.

An open­-label, investigator ­initiated Phase 2 study (ClinicalTrials.gov identifier NCT03157037) in severe anti­-GBM antibody disease with imlifidase is ongoing. As of March 31, 2019, eight patients with this ultra­rare disease of the targeted 15 patients have been enrolled in the Phase 2 study, which aims to evaluate the safety and tolerability of imlifidase, and to assess efficacy based on renal function at six months after treatment.

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